Oxidative damage to specific neurons in the central nervous system (CNS) is a commonly observed pathophysiologic feature of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). A wide range of oxidative damage to cellular macromolecules in nigrostriatal dopaminergic neurons, including lipids, proteins, and nucleotides, has been observed in postmortem brains of PD patients. The molecular mechanism underlying selective susceptibility of the nigrostriatal pathway to oxidative stress remains unresolved. Mitochondrial dysfunctions, including selective decrease in respiratory complex I activity and mitochondrial DNA abnormality (Bender et al. 2006, Schapira et al. 1989), are implicated in the pathogenesis of PD partly through an increase in the production of the reactive oxygen species (ROS). Moreover, a significant increase in oxidative damage to DNA in both nucleus and mitochondria has been observed in dopaminergic neurons in the substantia nigra (SN) of PD patients (Alam et al. 1997, Migliore et al. 2002, Sherer et al. 2005). However, the mechanisms of DNA damage, especially nuclear DNA damage, are obscure.